鸟白血病病毒J亚群(ALV-J)引起多种与肿瘤形成、生育能力下降和诱导免疫抑制疾病有关的疾病，导致全球家禽产业面临重大的经济损失。病毒通常利用宿主细胞机制进行复制。虽然有越来越多的证据显示细胞蛋白参与病毒复制，但ALV-J与宿主蛋白之间在病毒生命周期的关键步骤上的相互作用仍不清楚。在这里，我们报告了核糖核苷酸二磷酸还原酶亚单位M2（RRM2）通过与壳蛋白P27相互作用并激活Wnt/β-连环信号通路在ALV-J感染过程中起到关键作用。我们发现，在ALV-J感染过程中，RRM2的表达得到有效增加，并且RRM2通过与病毒壳蛋白P27相互作用促进ALV-J的复制。此外，ALV-J的P27通过促进β-连环蛋白进入细胞核激活Wnt/β-连环信号通路，而RRM2通过增强其在Ser18的磷酸化来激活Wnt/β-连环信号通路。这些数据表明，ALV-J感染通过上调RRM2表达有利于病毒在宿主细胞中的复制，进而激活Wnt/β-连环信号通路。 IMPORTANCE 我们的研究结果揭示了RRM2促进ALV-J生长的一种新机制：ALV-J感染通过上调RRM2表达有利于病毒通过与壳蛋白P27的相互作用并激活Wnt/β-连环通路在宿主细胞中进行复制。此外，我们验证了RRM2在位于18位丝氨酸的磷酸化是调节Wnt/β-连环信号通路激活的重要因素。本研究为进一步研究ALV-J感染的分子机制提供了见解。

Avian leukemia virus subgroup J (ALV-J) causes various diseases associated with tumor formation and decreased fertility and induced immunosuppressive disease, resulting in significant economic losses in the poultry industry globally. Virus usually exploits the host cellular machinery for their replication. Although there are increasing evidences for the cellular proteins involving viral replication, the interaction between ALV-J and host proteins leading to the pivotal steps of viral life cycle are still unclear. Here, we reported that ribonucleoside-diphosphate reductase subunit M2 (RRM2) plays a critical role during ALV-J infection by interacting with capsid protein P27 and activating Wnt/β-catenin signaling. We found that the expression of RRM2 is effectively increased during ALV-J infection, and that RRM2 facilitates ALV-J replication by interacting with viral capsid protein P27. Furthermore, ALV-J P27 activated Wnt/β-catenin signaling by promoting β-catenin entry into the nucleus, and RRM2 activated Wnt/β-catenin signaling by enhancing its phosphorylation at Ser18 during ALV-J infection. These data suggest that the upregulation of RRM2 expression by ALV-J infection favors viral replication in host cells via activating Wnt/β-catenin signaling. IMPORTANCE Our results revealed a novel mechanism by which RRM2 facilitates ALV-J growth. That is, the upregulation of RRM2 expression by ALV-J infection favors viral replication by interacting with capsid protein P27 and activating Wnt/β-catenin pathway in host cells. Furthermore, the phosphorylation of serine at position 18 of RRM2 was verified to be the important factor regulating the activation of Wnt/β-catenin signaling. This study provides insights for further studies of the molecular mechanism of ALV-J infection.